The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis

Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications.To enhance the sensitivity and selectivity,the combination of the fluorescent nanoparticles with the molecularly imprinted polymer,i.e.molecularly imprinted fluorescent nanoparticles(MIFN),was an effective way.The sensor based on MIFN(the MIFN sensor)could be more compatible with the complex sample matrix,which was especially widely adopted in medical and biological analysis.In this mini-review,the construction method,detective mechanism and types of MIFN sensors are elaborated.The current applications of MIFN sensors in pharmaceutical analysis,including pesticides/herbicide,veterinary drugs/drugs residues and human related proteins,are highlighted based on the literature in the recent three years.Finally,the research prospect and development trend of the MIFN sensor are forecasted.

Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

Monitoring NAD(H) and NADP(H) dynamics during organismal development with genetically encoded fluorescent biosensors

Cell metabolism plays vital roles in organismal development,but it has been much less studied than transcriptional and epigenetic control of developmental programs.The difficulty might be largely attributed to the lack of in situ metabolite assays.Genetically encoded fluorescent sensors are powerful tools for noninvasive metabolic monitoring in living cells and in vivo by highly spatiotemporal visualization.Among all living organisms,the NAD(H)and NADP(H)pools are essential for maintaining redox homeostasis and for modulating cellular metabolism.Here,we introduce NAD(H)and NADP(H)biosensors,present example assays in developing organisms,and describe promising prospects for how sensors contribute to developmental biology research.

Multifunctional N,S-doped and methionine functionalized carbon dots for on−off−on Fe^(3+)and ascorbic acid sensing,cell imaging,and fluorescent ink applying

Fluorescent carbon dots(CDs)have been identified as potential nanosensors and attracted tremendous research interests in wide areas including anti-counterfeiting,environmental and biological sensing and imaging in considering of the attractive optical properties.In this work,we present a CDs based fluorescent sensor from polyvinylpyrrolidone,citric acid,and methionine as precursors by hydrothermal approach.The selective quantifying of Fe^(3+)and ascorbic acid(AA)are based on the fluorescent on-off-on process,in which the fluorescent quenching is induced by the coordination of the Fe^(3+)on the surface of the CDs,while the fluorescence recovery is mainly attributed to redox reaction between Fe^(3+)and AA,breaking the coordination and bringing the fluorescence back.Inspired by the good water solubility and biocompatibility,significant photostability,superior photobleaching resistance as well as high selectivity,sensitivity,and interference immunity,which are constructed mainly from the N,S-doping and methionine surface functionalization,the CDs have not only been employed as fluorescence ink in multiple anticounterfeiting printing and confidential document writing or transmitting,but also been developed as promising fluorescence sensors in solution and solid by CDs doped test strips and hydrogels for effectively monitoring and removing of Fe^(3+)and AA in environmental aqueous solution.The CDs have been also implemented as effective diagnostic candidates for imaging and tracking of Fe^(3+)and AA in living cells,accelerating the understanding of their function and importance in related biological processes for the prevention and treatment specific diseases.

Ratiometric Fluorescence Detection of 6-Mercaptopurine Based on the Nanohybrid of Fluorescence Carbon Dots and Gold Nanoclusters

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed. The present work reports a sensitive and selective RF sensor for the detection of 6-mercaptopurine, by hybridizing carbon nanodots (CDots) and gold nanoclusters (AuNCs) capped with bovine serum albumin (BSA). The CDots serve as the reference signal and the AuNCs as the reporter. On addition of the 6-MP, AuNCs formed aggregates, because the existing cross-links within the AuNCs and BSA structure were broken in favour of the Au-S bonds, which can enhance the fluorescence of AuNCs, while the fluorescence of CDots is stable against 6-MP, leading to distinct ratiometric fluorescence changes when exposed to 6-MP. 6-MP could be detected in the range of 0 - 30.22 μM with a detection limit of 54 nM. The developed sensor was applied for the determination of 6-MP in human serum samples and satisfactory results were obtained.

Application of TIRFM in Biomolecule Research and Clinical Medicine

With the increasing demand for imaging quality, many scientists constantly explore new imaging instruments to meet the requirements. The total internal reflection fluorescence microscopy has some incomparable superiorities, so it has become one of the research hotspots in recent years. It can show great performance in single-molecule imaging because it has unique imaging principles. This apparatus is used mainly in two fields, biomolecule research and clinical medicine. To know this instrument’s function, the summary of applications in these two parts was given in this article. Now, scientists who have been focusing on this apparatus try to make this microscope combined with other late-model precise instruments that probe some unknown interaction mechanism of action. The TIRFM will show extraordinary talents in many aspects, and it will become a powerful tool for people to explore the mysteries of life.

Surfactant-regulated acetylpyrene assemblies as fluorescent probes for identifying heme proteins in an aqueous solution

Heme proteins play various important roles in a variety of physiological and pathological processes.Surfactant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins.In this study,an acetylpyrene fluorophore containing imidazole HP-1 was synthesized,and it could be well modulated by an anionic surfactant sodium dodecyl sulfate(SDS).The selected ensemble based on HP-1/SDS assemblies exhibited selective fluorescence sensing performance towards the heme proteins,including neuroglobin(Ngb),myoglobin(Mb)and cytochrome c(Cyt c).Besides,phospholipid DMPC vesicles as membrane models were particularly explored the association process between the heme protein Mb and membrane.The present work showed that Mb induced the lysis of DMPC liposomes visualized by transmission electron microscopy and optical microscope.

Fluorescence immunoassay based on alkaline phosphatase-induced in situ generation of fluorescent non-conjugated polymer dots

Alkaline phosphatase(ALP) activity assay is not only significant to the clinical diagnosis of some related disease, but also momentous to the construction of ALP-based enzyme-linked immunosorbent assay(ELISA). Herein, for the first time, we have discovered that ascorbic acid(AA) can specially react with N-methylethylenediamine(N-MEDA) to generate fluorescent non-conjugated polymer dots(NCPDs) under mild conditions. On the basis of the AA-responsive emission and ALP-catalyzed hydrolysis of ascorbic acid 2-phosphate(AA2P) to AA, we have exploited a fluorometric ALP activity assay with high sensitivity and selectivity. Furthermore, by means of conventional ALP-based ELISA platform, a conceptual fluorescent ELISA has been constructed and applied in the potential clinical diagnosis, during which cardiac troponin I(cTnI), a well-established biomarker of acute myocardial infarction, has been chosen as the model target. We envision that such original fluorescent NCPDs generation-enabled ELISA could become a versatile tool in biochemical sensing and medical diagnosis in the future.

Self-assembly of a quadrangular prismatic covalent cage templated by zinc ions:A selective fluorescent sensor for palladium ions

Herein we report a covalent cage TPE-Zn_(4)based on a tetraphenylethylene molecule via subcomponent self-assembly,which is templated by zinc ions.TPE-Zn_(4)features a quadrangular prismatic cage structure,which is characterized by NMR,mass spectrum,and single-crystal X-ray diffractions.TPE-Zn_(4)emitted orange fluorescence(λ_(em)=620 nm)in DMSO solution under the irradiation of UV light(λ_(ex)=395 nm)and can be applied as a fluorescence sensor for selectively detecting Pd^(2+).The fluorescence of TPE-Zn_(4)was quenched by Pd^(2+)in DMSO solution,and a very low detection limit of 62.3 n M was achieved.Mechanism studies reveal that the Pd^(2+)can replace the Zn^(2+),and the heavy atom effect and chelation-enhanced quenching effect between the Pd^(2+)and the cage probably cause the fluorescence quenching.

A simple fluorescent sensor for highly sensitive detection of UO_(2)2+

Extensive application of nuclear energy has caused widespread environmental uranium contamination.New detection approaches without complicated sample pretreatment and precision instruments are in demand for on-site and in-time determination of uranyl ions in environmental monitoring, especially in an emergency situation. In this work, a simple and effective fluorescent sensor(Z)-N’-hydroxy-4-(1,2,2-triphenylvinyl)benzimidamide(TPE-A) with aggregation-induced emission(AIE) character was established and studied. It could realize to detect UO_(2)2+via quenching the fluorescence of its aggregation-induced emission, with good selectivity and sensitivity. Such strategy shows a wide linear range from 5.0 × 10^(-8)mol/L to 4.5 × 10^(-7)mol/L(R^(2)= 0.9988) with exceptional sensitivity reaching 4.7 × 10^(-9)mol/L, which is far below the limit for uranium in drinking water(30 μg/L, ca. 1.1 × 10-7mol/L) stipulated by the WHO.A response time less than four minutes make it rapid for uranyl ion measurement. It was applied for detection of uranyl ion in spiked river water samples with recoveries in the range of 98.7%-104.0%, comparable to those obtained by ICP-MS. With the advantages of portable apparatus, rapid detection process and high sensitivity, TPE-A can serve as a promising fluorescent sensor for the detection of UO_(2)2+in environmental water samples.

Bi-ortho-Carborane Unit-Riveted Perylene Monoimides:Structure-Tuned Optical Switches for Electron Transfer and Robust Thin Film-Based Fluorescence Sensors

Innovative design of sensing fluorophores possessing superior photophysical properties,porosity,and packing-resistance structures is pivotal for high performance film-based fluorescent sensors.Herein,PDCB,a perylene monoimide(PMI)derivative incorporating large spatial phenyl-carborane was synthesized and found to exhibit unexpected photophysical properties.The structurally bent PDCB exhibits not only PMI-like emission but also a red-shifted emission.In sharp contrast,PMI-CBH,a linear PMI derivative,exhibits only PMI-like emission.Furthermore,upon local excitation,PDCB undergoes a photoinduced electron transfer(PET)between PMI and phenylcarborane,resulting in a charge-transfer state.Two other PMI derivatives,PCB and PDCBP,showed a similar phenomenon.The PET rate is in the order of PCB(48 ps^(-1))>PDCB(163 ps^(-1))>PDCBP(815 ps^(-1))in toluene,which decreases with increasing steric hindrance,inferring structure reorganization prior to the PET process.As expected,a fabricated PDCB-based sensor showed excellent performance in acetone sensing.

A fluorescent film sensor for high-performance detection of Listeria monocytogenes via vapor sampling

Foodborne Listeria monocytogenes poses serious threats to public health.Fast and sensitive detection of the pathogen at the point of contamination is thus crucial to halt the spread of bacteria-related diseases.Herein,we report for the first time a fluorescent film sensor to detect the biomarker of L.monocytogenes,3-hydroxy-2-butanone.The sensor demonstrated unprecedented sensing performance for the analyte with a detection limit lower than 0.05 mg/m^(3),response time less than 1 s,full reversibility,and excellent selectivity.Further study showed that the sensor can be used to monitor the growth of L.monocytogenes with much-improved sensitivity.The superior performance of the sensor is ascribed to the specific binding,efficient charge transfer emission,and porous adlayer structure of the specially designed sensing fluorophore-based film.Our work paves the way to develop a portable detector to meet the needs for on-site and real-time detection of foodborne pathogens.

A mini-review on MXenes as versatile substrate for advanced sensors

MXenes have emerged as versatile 2D materials that are already gaining paramount attention in the areas of energy,catalyst,electromagnetic shielding,and sensors.The unique surface chemistry,graphene-like mo rphology,high hydrophilicity,metal-like conductivity with redox capability identifies MXenes,as an ideal material for surface-related applications.This short review summarizes the most recent reports that discuss the potential application of MXenes and their hybrids as a transducer material for advanced sensors.Based on the nature of transducing signals,the discussion is categorized into three sections,which include electrochemical(bio)sensors,gas sensors,and finally,electro-chemiluminescence&fluorescent sensors.The review provides a concise summary of all the analytical merits obtained subsequent to the use of MXenes,followed by endeavors that have been made to accentuate the future perspective of MXenes in sensor devices.

Surface engineering of carbon dots for highly sensitive α-glucosidase assay and inhibition evaluation

Monitoringα-glucosidase(α-Glu)activity is of great significance for the early diagnosis of typeⅡdiabetes.Here the blue fluorescent carbon dots(CDs)were integrated with two different recognizing molecules,β-cyclodextrin and phenylboronic acid,for assembling a multifunctional CDs(mCDs)nanoplatform for sensitively analyzingα-Glu and its inhibitors.The hydrolyzed product of 4-nitrophenyl-α-D-glucopyranoside(α-Glu substrate),p-nitrophenol,could efficiently quench the fluorescence of mCDs due to its cooperative molecular recognition withβ-cyclodextrin and phenylboronic acid.The mCDs could be utilized for the detection ofα-Glu activity with the limit of detection of 0.030 U/L.Moreover,the presentα-Glu detection platform revealed a high selectivity,and other natural enzymes showed scarcely any effect on the present mCDs system.The proposed method could be facilely used to screenα-Glu inhibitors with satisfying performance.The rational mCDs is expected to supplement more comprehensive biosensing platforms for highly sensitive and specific recognition of disease-relevant biomarkers with clinical importance.

Comparison of Two Rhodamine-Polyamine Polystyrene Solid-phase Fluorescence Sensors for Hg(Ⅱ) Detection Based on Theoretical Calculation

Two novel rhodamine-based polystyrene solid-phase fluorescence sensors PS-PA-Ⅰ and PS・PA-Ⅱ with different lengths of polyamines were synthesized for Hg(Ⅱ)determination.Thedetection mechanism involving the Hg(Ⅱ)chelation-induced spirocycle open of rhodamine was proposed with the aid of theoretical calculation.The stronger N—Hg bond and the longer polyamine chain in PS-PA-Ⅱ led to a better selectivity,much higher and more quickly fluorescence response to Hg(Ⅱ).

Effects of the molluscicide can didate PPU06 on alkaline phosphatase in the golden apple snails determined using a near-infrared fluorescent probe

We constructed a reaction-based near-infrared fluorescent probe(Niap) to specifically identify alkaline phosphatase(ALP) with fast red fluorescence enhancement.Based on the positive concentrationdependent manner between the fluorescent intensity of the Niap and ALP,probe Niap was used to study the ALP enrichment and variation in golden apple snails(Pomacea canaliculata) exposed to the molluscicide candidate PPU06.After treatment with different concentrations of PPU06 over various times,three organs of the surviving snails,liver,stomach and plantaris,were frozen and sectioned for fluorescent imaging experiments.With increased PPU06 concentration,red fluorescence substantially increased in the liver and reached a maximum within 24 h when the PPU06 co ncentration was 0.75 mg/L.No obvious changes in the stomach or foot plantaris were found.It showed PPU06 caused liver injury and stimulated the increase of ALP in the liver of P.canaliculata.This study demonstrates a rapid ALP fluorescent identification method that can be used to study the effects of PPU06 on P.canaliculata.It also provides optical evidence that may aid in the discovery of new chemistry for snail control.

A GSH-responsive PET-based fluorescent probe for cancer cells imaging

An efficient PET-based probe,in which the ferrocene quencher and the naphthalimide fluorophore are linked by a disulfide bond,has been developed.This probe can be activated by GSH with fluorescence a turn-on response for blocking the PET process.In addition,it was successfully applied for distinguishing cancer cells from normal cells。

Pyrenoviologen-based fluorescent sensor for detection of picric acid in aqueous solution

Two highly emissive pyrenoviologen derivatives were synthesized and used to fabricate fluorescent sensors for detection of picric acid(PA)with good sensitivity and selectivity.The sensitivity of the sensor was attributed to the specific electrostatic association effect of the cationic pyrenoviologens to the picrate anions,which also gave the sensor special selectivity among other compounds with similar structure.The electron transfer between them was attributed to the fluorescence response.Fluorescence lifetime measurements revealed that the quenching is static in nature.The novel and efficient pyrenoviologen derivatives-based sensors offered a strategy to fabricate real-life PA sensor.

A Highly Selective and Turn-on Fluorescent Probe for Fe^(3+) Ion Based on Perylene Tetracarboxylic Diimide

We have demonstrated a turn-on fluorescent sensor 6 for detection of Fe^(3+) based on photo-induced electron transfer(PET)mechanism.The probe comprises a perylene tetracarboxylic diimide(PDI)fluorophore and two bis((1,2,3-triazol-4-yl)methyl)amine(DTA)moieties as the metal ion receptors.It exhibits high selectivity toward Fe^(3+) over various other metal ions in CH_(3)CN/H_(2)O(1∶1,V/V).The binding stoichiometry for 6-Fe^(3+) complexes has been determined to be 1∶2 by a Job plot of fluorescence.The association constant between 6 and Fe^(3+) was estimated to be 1.04×10^(10)(mol/L)^(−2) by Benesi-Hildebrand equation.